Gene profiling of Graffi murine leukemia virus-induced lymphoid leukemias: identification of leukemia markers and Fmn2 as a potential oncogene

Blood. 2011 Feb 10;117(6):1899-910. doi: 10.1182/blood-2010-10-311001. Epub 2010 Dec 6.

Abstract

The Graffi murine leukemia virus induces a large spectrum of leukemias in mice and thus provides a good model to compare the transcriptome of all types of leukemias. We analyzed the gene expression profiles of both T and B leukemias induced by the virus with DNA microarrays. Given that we considered that a 4-fold change in expression level was significant, 388 probe sets were associated to B, to T, or common to both leukemias. Several of them were not yet associated with lymphoid leukemia. We confirmed specific deregulation of Fmn2, Arntl2, Bfsp2, Gfra2, Gpm6a, and Gpm6b in B leukemia, of Nln, Fbln1, and Bmp7 in T leukemias, and of Etv5 in both leukemias. More importantly, we show that the mouse Fmn2 induced an anchorage-independent growth, a drastic modification in cell shape with a concomitant disruption of the actin cytoskeleton. Interestingly, we found that human FMN2 is overexpressed in approximately 95% of pre-B acute lymphoblastic leukemia with the highest expression levels in patients with a TEL/AML1 rearrangement. These results, surely related to the role of FMN2 in meiotic spindle maintenance, suggest its important role in leukemogenesis. Finally, we propose a new panel of genes potentially involved in T and/or B leukemias.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Animals
  • Biomarkers, Tumor / genetics
  • Child
  • Core Binding Factor Alpha 2 Subunit / genetics
  • Formins
  • Gene Expression Profiling
  • Genetic Markers
  • Humans
  • Leukemia Virus, Murine / pathogenicity*
  • Leukemia, Experimental / genetics*
  • Leukemia, Experimental / metabolism
  • Leukemia, T-Cell / genetics
  • Mice
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism
  • Nerve Tissue Proteins / genetics
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Oncogene Proteins, Fusion / genetics
  • Oncogenes*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Retroviridae Infections / genetics*
  • Retroviridae Infections / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Virus Infections / genetics*
  • Tumor Virus Infections / metabolism

Substances

  • Biomarkers, Tumor
  • Core Binding Factor Alpha 2 Subunit
  • Formins
  • Genetic Markers
  • Microfilament Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Oncogene Proteins, Fusion
  • TEL-AML1 fusion protein
  • formin 2 protein, mouse